Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000670181 | SCV000795008 | uncertain significance | Retinitis pigmentosa 25 | 2017-10-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001362404 | SCV001558418 | likely pathogenic | not provided | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2790 of the EYS protein (p.Arg2790Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of retinitis pigmentosa (PMID: 28041643; Invitae). ClinVar contains an entry for this variant (Variation ID: 438209). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on EYS protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282186 | SCV002571822 | uncertain significance | not specified | 2022-08-01 | criteria provided, single submitter | clinical testing | Variant summary: EYS c.8368A>G (p.Arg2790Gly) results in a non-conservative amino acid change located in the Laminin G domain (IPR001791) of the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 156774 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.8368A>G has been reported in the literature in at-least one compound heterozygous individual reportedly diagnosed with Retinitis Pigmentosa (example: Carss_2017). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three submitters provided clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=2) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance |
| NIHR Bioresource Rare Diseases, |
RCV000505047 | SCV000599166 | likely pathogenic | Retinitis pigmentosa | 2015-01-01 | no assertion criteria provided | research |